Location matters: Attributing cognitive symptoms to white matter hyperintensities in 3,481 memory clinic patients

Background and aim: In memory clinic patients, assessing diagnostic relevance of white matter hyperintensities (WMHs), as a marker to explain cognitive deficits, can be challenging. Here, we aimed to quantify this relevance by measuring the variance in cognitive function they explain, and consider, beyond total WMH volume, WMH location in specific tracts and normative WMH values.

Methods

We analyzed previously pooled and harmonized individual patient data (n=3,481, 71±9 years old, 50% females) from 11 international memory clinic cohorts from the Meta-VCI-Map consortium. Cognitive function was assessed in 4 domains: attention and executive function, information processing speed, verbal memory and language. We measured WMH volumes in 20 white matter tracts. These were also norm-adjusted for age and sex, using normative WMH values from 14,876 community-dwelling individuals. Explained variance in cognitive function was measured for demographics only (age, sex and education) and demographics combined with total WMH volume, tract-specific WMH volumes and norm-adjusted and tract-specific WMH z-scores.